PB1942: PARTIAL RESPONSE WITH LYMPHOCYTOSIS (PR-L) IS NOT APPLICABLE FOR ACALABRUTINIB. AN ITALIAN MULTICENTER EXPERIENCE OF REAL LIFE.
Authors: Idanna Innocenti, Antonio Mosca, Annamaria Tomasso, Andrea Galitzia, Lydia Scarfò, Eugenio Galli, Roberta Laureana, Giulia Benintende, Veronica Mattiello, Francesca Morelli, Sabrina Chiriu, Maria Ilaria Del Principe, Giulia Zamprogna, Massimo Gentile, Nicole Fabbri, Francesco Autore, Paolo Sportoletti, Alberto Fresa, Gioacchino Catania, Marta Coscia, Alessandra Tedeschi, Alessandro Sanna, Marzia Varettoni, Paolo Ghia, Roberta Murru, Luca Laurenti
Journal: HemaSphere (2023)

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: Increased absolute lymphocyte count (ALC) characterizes chronic lymphocytic leukemia (CLL), and it is also observed in the first phase of treatment with Ibrutinib (IBR), the “first-in-class” Bruton’s tyrosine kinase inhibitor (BTKi), independently of previous lines of treatment. The IBR induced lymphocytosis, which is due to a redistribution of lymphocytes from the neoplastic nodal compartment into the peripheral blood, is observed in 57% of patients treated in first line, and it is higher in IgHV mutated CLL. Prolonged lymphocytosis likely represents the persistence of a quiescent clone. This phenomenon is transient in most patients, resolving within 8 months, but can rarely persist over 12 months, without impact on survival. Despite lymphocytosis in IBR has been widely investigated, little is known about the presence and duration of lymphocytosis in patients treated with Acalabrutinib (Acala). Aims: The main purpose of this study is defining kinetics, timing, and impact of drug-induced lymphocytosis during treatment of CLL patients with Acala or IBR, to underline possible differences in terms of entity and duration of the lymphocytosis. Methods: In our retrospective study, we enrolled 181 patients (114 male and 67 female), treated in first line with BTKi monotherapy (111 IBR and 70 Acala), from 12 different Italian centers, with last follow up in January 2023. For each patient we collected data about the burden of disease at baseline (in terms of staging, adenopathy and splenomegaly), the biological features of the disease (cytogenetic aberrations and molecular mutations, IgHV mutational status) and the ALC at the baseline and at well-defined time-point (1-2- 3- 6- 9- 12 months) over an observational period of 1 year (Table 1). Results: We observed a median ALC increase after the beginning of therapy both in the IBR and in the Acala group. Median lymphocytosis was higher than baseline during the first months of treatment in both cohorts. A progressive decrease in median ALC occurred after the second month of treatment in both groups: at this time-point, median lymphocytes count was 70% of baseline in Acala cohort vs 81.5% in IBR cohort (p 0.049). From 6th month to the end of the study, we found statistical differences in the ALC with higher counts in IBR. At 6th months, median ALC was 5700/microL in Acala vs 10200/microL in IBR group, at 9th 3800/microL vs 8070/microL and at 12th 2600/microL vs 5150/microL (Table 1). Summary/Conclusion: Acala can determine, like IBR, an increase of ALC immediately after starting therapy. Therefore, lymphocytosis appears as a BTKi-class effect. Despite this, the kinetics of lymphocytosis are not overlapping when comparing the two drugs. From the 6th month, the ALC reached almost-normal values in Acala group, with significantly statistical differences compared to IBR. These data suggest that the response criterion of PR-L may not be applicable for Acala.Keywords: Bruton’s tyrosine kinase inhibitor (BTKi), Absolute lymphocyte count, B-CLL